This project deals with the interactions between EBV-infected cells and the host immune system in normal and immunodefective persons. For an improved understanding of this complex system, it is necessary to broaden our knowledge both on the interaction of the virus with different host cells in vitro and in vivo, and on the interplay between the virally infected cells and the host. This project aims at the analysis of certain questions at both levels, in a mutually interrelated way. The project consists of the following parts: I. Analysis of the virus-cell-host system II. Clinically related studies Antigenic analysis will focus on the role of the newly detected membrane antigen on the surface of transformed, proliferating, non-virus producer cells, its immune recognition, its genetic determination mechanism (in relation to the viral genome) and the significance of blocking antibodies directed against it. Effector analysis will disssect the role of various lymphocyte subtypes and mediators in BL and NPC, immunodefectives with and without EBV-carrying lymphoproliferative disease, and in healthy controls. At the target cell level, continued attention will be given to the role of spontaneous or induced B-cell differentiation by immunological and non-immunological host control. The clinically related studies wil focus on the monoclonal vs. polyclonal nature of EBV-transformed B-cell proliferation in transplant lymphomas, and lymphoproliferative disease in XLP, as it relates to EBV. At the effector level, we shall continue to investigate the impairment of different effectors and the role of suppression in immunodeficient EBV-carrying lymphomas, as contrasted to immunodefective states (HD and NHL, AT) with an impaired control of EBV-transformed cells (as indicated by the dissociation of sensitization and antibody formation into EBNA, on the one hand, and to EA/VCA on the other), but without EBV carryig lymphoproliferative disease. A special effector and target cell study will be carried out on pre-AIDS lymphomas.